Abstract
Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Aβ1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau181p) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ1-42, t-tau, and p-tau181p and apolipoprotein E (ApoE) ε4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Aβ1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ1-42 levels and higher tau levels supports the hypothesis that CSF Aβ1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1340-1354 |
| Number of pages | 15 |
| Journal | Neurobiology of Aging |
| Volume | 31 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2010 |
Fingerprint
Keywords
- Alzheimer's disease
- ApoE
- Atrophy
- Biomarkers
- Brain tissue volume
- Cerebrospinal fluid
- Cortical thickness
- Healthy aging
- Mild cognitive impairment
- MRI
ASJC Scopus subject areas
- Neuroscience(all)
- Aging
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology
Cite this
Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile : A longitudinal MRI study. / Tosun, Duygu; Schuff, Norbert; Truran-Sacrey, Diana; Shaw, Leslie M.; Trojanowski, John Q.; Aisen, Paul; Petersen, Ronald Carl; Weiner, Michael W.
In: Neurobiology of Aging, Vol. 31, No. 8, 01.08.2010, p. 1340-1354.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile
T2 - A longitudinal MRI study
AU - Tosun, Duygu
AU - Schuff, Norbert
AU - Truran-Sacrey, Diana
AU - Shaw, Leslie M.
AU - Trojanowski, John Q.
AU - Aisen, Paul
AU - Petersen, Ronald Carl
AU - Weiner, Michael W.
PY - 2010/8/1
Y1 - 2010/8/1
N2 - Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Aβ1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau181p) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ1-42, t-tau, and p-tau181p and apolipoprotein E (ApoE) ε4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Aβ1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ1-42 levels and higher tau levels supports the hypothesis that CSF Aβ1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.
AB - Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Aβ1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau181p) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ1-42, t-tau, and p-tau181p and apolipoprotein E (ApoE) ε4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Aβ1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ1-42 levels and higher tau levels supports the hypothesis that CSF Aβ1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.
KW - Alzheimer's disease
KW - ApoE
KW - Atrophy
KW - Biomarkers
KW - Brain tissue volume
KW - Cerebrospinal fluid
KW - Cortical thickness
KW - Healthy aging
KW - Mild cognitive impairment
KW - MRI
UR - http://www.scopus.com/inward/record.url?scp=77954030909&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954030909&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2010.04.030
DO - 10.1016/j.neurobiolaging.2010.04.030
M3 - Article
C2 - 20570401
AN - SCOPUS:77954030909
VL - 31
SP - 1340
EP - 1354
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 8
ER -